Many clinical diseases are associated with abnormal regulation of the immune system. The regulation of many events in immune reactions is often controlled by suppressor cells. Abnormal suppressor cell function has been associated with autoimmune diseases in both humans and animal models. We have developed a model of selective suppressor cell loss in NZB/WF1 mice which is associated with a marked acceleration of a lupus erythematosus-like disease. This project is designed to study the effects of suppressor cell loss in a "normal" mouse strain not predisposed to the development of autoimmune disease. We have shown that NZB and NZB/W mice have a loss of non-specific suppressor cells but that the development of alloantigen-specific suppressor cells is normal. This suggests that at least two general types of suppressor mechanisms exist in immune regulation and that the defect in the autoimmune mice involves only a portion of the regulatory mechanism. The role that both non-specific suppression and alloantigen-specific suppression may play in developing clinical disease is under study. Treatment of normal mice (CDF1) with selected lots of a naturally occurring thymocytotoxic antibody (NTA) causes a defect in non-specific suppressor function but leaves alloantigen-specific suppressor function intact. The role that this induced defect plays in the loss of self-tolerance and/or the development of clinical disease is being investigated.